Apelin peptides, antibodies thereto, and methods of use

Abstract

The present disclosure concerns the use of biologically active apelin peptides and compositions that are processed from larger precursor proteins and further post-translationally modified to influence cell growth. Particular methods are useful for promoting cell growth, while others are particularly useful for inhibiting cell growth.

We claim: 
     
         1 . An isolated antibody that binds to an epitope specific to salcut-NH 2  polypeptide (SEQ ID NO: 19), which isolated antibody does not bind to apelin-36 (42-77), apelin-17 (61-77), or apelin-13 (65-77). 
     
     
         2 . A method of treating a tumor or a disease caused by abnormal angiogenesis of a subject, comprising administering to the subject a therapeutically effective amount of the isolated antibody of  claim 1 , wherein the subject has a tumor or a disease caused by abnormal angiogenesis and administration of the polypeptide modifies tumor cell growth or endothelial cell growth in the subject, thereby treating the tumor or disease caused by abnormal angiogenesis of the subject. 
     
     
         3 . The method of  claim 2 , wherein the disease caused by abnormal angiogenesis comprises neoplasia, cardiovascular disease, peripheral vascular disease, hypertension, preeclampsia syndrome, abnormal angiogenesis, diabetes, ocular degeneration, idiopathic pulmonary fibrosis, wound healing, altered mast cell migration, chronic obstructive pulmonary disease, inflammatory diseases such as arthritis (juvenile and rheumatoid) and inflammatory bowel disease, cardiovascular disease, avascular or ischemic insult, myocardial infarction, stroke, vasculititis/angiitis, systemic or vascular sclerosis, gangrene, congelation (severe frostbite), alopecia, eczema, ulcers, lymphedema (parasite induced, for example elephantiasis/elephantitis, or tumor induced), vascular hyperplasia, hemangioma, diabetic induced retinopathy, macular degenerative disease, psoriasis, or endometriosis. 
     
     
         4 . The antibody of  claim 1 , wherein the antibody is a monoclonal antibody. 
     
     
         5 . The antibody of  claim 4 , wherein the monoclonal antibody is humanized. 
     
     
         6 . A method of modulating cell growth, comprising administering isolated salcut-NH 2  polypeptide (SEQ ID NO: 19) to a cell sample, thereby modulating cell growth. 
     
     
         7 . The method of  claim 6 , wherein cell growth is increased. 
     
     
         8 . The method of  claim 6 , wherein the cell growth is decreased. 
     
     
         9 . The method of  claim 6 , wherein the cells comprise endothelial cells or tumor cells. 
     
     
         10 . The method of  claim 6 , wherein the cell sample is in vivo. 
     
     
         11 . An inhibitor of cell growth modulating activity of salcut-NH 2  polypeptide (SEQ ID NO: 19), comprising a peptide or neutralizing antibody. 
     
     
         12 . A method of treating a tumor or a disease caused by abnormal angiogenesis of a subject, comprising administering to the subject a therapeutically effective amount of the inhibitor of  claim 11 , wherein the subject has a tumor or a disease caused by abnormal angiogenesis and administration of the inhibitor modifies tumor cell growth or endothelial cell growth in the subject, thereby treating the tumor or disease caused by abnormal angiogenesis of the subject. 
     
     
         14 . An activator of cell growth modulating activity of salcut-NH 2  polypeptide (SEQ ID NO: 19), comprising a peptide or activating antibody. 
     
     
         15 . A method of treating a disease caused by abnormal angiogenesis of a subject, comprising administering to the subject a therapeutically effective amount of the activator of  claim 14 , wherein the subject has a disease caused by abnormal angiogenesis and administration of the activator modifies endothelial cell growth in the subject, thereby treating the disease caused by abnormal angiogenesis of the subject.